Manipulating particulate matter

ABSTRACT

An acoustic standing wave is established in a fluid medium with a varying energy density in its nodal planes. Particles in the fluid medium responsive to the acoustic energy accumulate at these nodal planes and by the action of the variations of energy density in conjunction with the fluid viscous forces and/or field forces acting in the direction of the nodal planes, the movement of the particles held at these planes can be controlled. The adverse effects of attenuation of the acoustic beams producing the standing wave are reduced in this system, because any streaming due to imbalance of the acoustic forces forming the standing wave does not act in the direction in which the movement of the particles can be controlled.

This invention relates to the manipulation of particulate matter in afluid medium by the use of ultrasonic wave energy, including thesegregation of dissimilar particles from a mixture of particles.

Standing waves generated by acoustic energy sources have been used in avariety of ways to influence the behaviour of particles suspended influids, it being known that particles can be attracted to the nodes ofthe standing wave. In essence the attracted particles becomesconcentrated at the nodal planes lying normal to the axis of propagationof the standing wave. At this juncture it should be said that thedetailed theory underlying the observed phenomenon of standing waves andtheir effect of particles is not fully understood, in particular thefactors influencing whether any given particle type tends to accumulateat the nodes or at the antinodes are unclear. However, this lack oftheoretical understanding has no bearing on the practical application ofthe present invention and throughout this specification the terms nodesand nodal planes are used to include references to both nodes andantinodes, because in practice it does not appear to matter whether anygiven particle type collects at one or the other.

If a standing wave is moved along its axis, the particles attracted tothe nodes can be carried through the fluid while they remain attached tothe standing wave: this is proposed, for example, in G.B. 2098498A. Inaddition, it is found that particles with different acoustic properties,in particular particles with different sizes and densities, can bedifferently affected by the acoustic energy of a standing wave and ithas been proposed to use ultrasonic frequencies to manipulate particlesin a chromatographic analytical procedure, to separate differentparticle types. In U.S. Pat. No. 4,280,823 it is suggested that astanding wave can function as the plates of a conventionalchromatographic column by retaining different particles at its nodes fordifferent times, the particles being carried through the standing waveby a gas flow directed axially along it.

There may also be mentioned the apparatus described in U.S. Pat No.4,523,632 (Barmetz et al) in which particles of different types areseparated to some degree as they are carried by a liquid flow along thelength of a horizontal chamber in which a standing wave is establishedwith a wavelength that is half the height of the chamber. This resultsin a so-called force potential well in the mid-height region of thechamber in which the particles will tend to concentrate. The gravityforces on the particles cause some degree of vertical separation of thedifferent types of particle, i.e. each type of particle will be locatedat a particular height representing an equipotential plane, dependentupon the influence of gravity on that particle type.

It is a characteristic of all these earlier proposals that controls ormanipulation of particles attracted to the nodes relies on the acousticforces acting on the particles in dependence upon the distance from eachnode, i.e. axially along the standing wave. One of the difficultieswhich exists in such a system and which becomes particularly acute atthe higher ultrasonic frequency ranges suitable for processing smallerparticles is that attenuation occurs in the energy propagated from theultrasound source. Divergence of the beam accentuates this effect. Thereis therefore an energy density gradient experienced by the fluid as aundirectional force, in effect a radiation pressure, which above aminimal value, produces movement of the fluid away from the radiationsource. This movement of fluid, referred to herein as acousticstreaming, clearly can have a disturbing influence on any attempt tocontrol the movement of particles by means of the acoustic forces actingdirectly on them, and especially if those acoustic forces are employedto discriminate between different particle types.

If a standing wave is formed in a body of fluid by a coaxial reflectionof ultrasonic radiation from a single source, there will be a radiationpressure acting on the fluid throughout the field of the standing wavegenerating acoustic streaming. By using two opposed ultrasonictransducers to establish a standing wave by the interference betweentheir outputs it is possible to balance out radiation pressure insubstance, over a minor part of the distance between the sources. For astanding wave in water at 20° C., the following Table shows the totalworking distance available in mm with three different tolerance levelsof imbalance for different frequencies, assuming a parallel acousticbeam:

                  TABLE 1                                                         ______________________________________                                                      Total working                                                                 distance available (mm)                                                       Percent imbalance                                               Frequency MHz   596           296      1%                                     ______________________________________                                        0.3             11,400        4,400    2,200                                  1.0             1,000         400  200                                        3.0             114           44   22                                         10.0            10.3          4    2                                          ______________________________________                                    

Thus, at 3 MHz in water, 22 mm is available on either side of the pointof exact energy balance if a maximum imbalance of 2% is acceptable,giving a maximum total working distance of 44 mm. As is clear from theTable the working distance available is increasingly restricted withrise of frequency, and this is the most significant single limitation onthe use of higher frequencies.

Another factor is that while experimental work shows that, although itis possible to accept a degree of imbalance before this causesnoticeable acoustic streaming, the volume available for a continuousprocess of discrimination between different types of particles by theuse of ultrasound is inevitably limited by this phenomenon. It thereforebecomes impractical to reduce the separation time for different particletypes by increasing the volume of the working vessel, since theseparation rate can only be increased in proportion to the square of thelinear dimension.

The present invention is based upon the novel concept that, by means ofnon-uniform acoustic energy intensities in a nodal plane of a standingwave, it is possible to provide an alternative method of manipulatingparticles in a fluid medium which alleviates the problem of acousticstreaming and allows other advantages to be achieved as compared withthe previously proposed methods which relay on controlling movement ofthe particles normal to a nodal plane.

According to one aspect of the invention, there is provided a method ofmanipulating particles in a fluid medium in which an ultrasonic standingwave is establishd in the fluid, said standing wave having a varyingenergy intensity in its nodal plane or planes in the fluid, the standingwave characteristics being chosen so as to accumulate at least a portionof the particles at the nodal plane or planes and the movement of saidparticles in the nodal plane or planes being controlled by means of thefluid viscous forces and/or field forces having at least a componentacting in the direction of said plane or planes.

According to another aspect of the invention, there is providedapparatus for manipulating particles in a fluid medium comprising achamber for containing the fluid with the particles suspended in it andmeans for generating an ultrasonic standing wave in the chamber, meansfor giving said standing wave a non-uniform energy intensity in itsnodal plane or planes in at least a part of the volume of said chamber,whereby to control the movement of at least a proportion of theparticles in a direction parallel to said nodal plane or planes by theaction of said varying energy density in conjunction with fluid viscousforces and/or field forces having at least a component acting on theparticles in the direction of said nodal plane or planes.

Convenient means of creating the non uniform energy intensity includethe use of screens which create acoustic shadows, or generatediffraction or focusing effects. It may be sufficient, however, simplyto rely on the non uniformity of an acoustic beam, in particular at itsedges.

In practice the variation of energy intensity will usually be producedas a repeated pattern moving relative to the fluid medium in the nodalplane, which will be termed herein a "nodal wave".

Nodal waves will be generated by providing an array of energy gradientsnormal to the ultrasound propagation axis and moving the array along anodal plane relative to the fluid in which the waves are propagated. Theparticles influenced by the acoustic energy thus move normal to the axisof the ultrasonic radiation which means that the length of the activezone in a working vessel is not limited by the ultrasound frequency.Attenuation does not occur in the direction of displacement of theenergy gradients, so that with increase of scale the rate of separationcan match the increase of working volume. Moreover, attenuation is lesscritical because a greater degree of imbalance will generally beacceptable in opposing beams operating normal to the plane of particlemovement, since the residual streaming of the fluid does not act in thedirection in which separation is occurring.

The use of nodal waves can allow considerable freedom in terms ofvariation of the level of the acoustic forces acting in different partsof a space, i.e. it is possible for nodal waves to be moved at differentrates and operate with different intensities in different regions. Bothtemporal and spatial variations in velocity may be used.

The nodal plane or planes will usually lie parallel to opposed walls ofa working vessel normal to the ultrasound propagation axis, and thegeometry may be so arranged that these walls--possibly formed by theacoustic transmission plates themselves--coincide with planes where thestanding wave is 180° out of phase with the nodes. Particles responsiveto the ultrasound are therefore automatically held away from the walls,so as to inhibit the trapping of particles by adhesion and/or boundarylayer effects.

The use of non-uniform energy densities in a nodal plane has so far beendiscussed in terms of energy density gradients that occur only along oneaxis, but it is possible to generate and make use of two-dimensionalnodal waves. Thus, with a standing wave having an axis of propagation inthe y direction, energy density gradients may be produced in a nodalplane in both the z and x directions.

In practical embodiments the nodal waves do not necessarily need to moverectilinearly. Particles in nodal waves may be moved in a curve and thusthe working vessel may be in the form of a coil or a body of revolution.In general, however, very long working paths will not be necessary sincethe nodal waves will have the all-or-none discrimination character ofany ultrasonic standing wave not unduly influenced by side effects suchas acoustic streaming, as the following discussion illustrates.

In an ideal (i.e. non-viscous) fluid in which an array of nodes isgenerated by the propagation of ultrasound such that each nodal surfacehas a uniform acoustic energy density, movement of a particle parallelto a nodal surface can occur without changing the net free energy of thesystem, that is, no work is done in the movement of the particle,assuming no field forces (e.g. gravitational or electromagnetic) areacting on the particle. If the energy density is not uniform, a forceproportional to the energy density gradient acts on the particle at thenode in a direction co-planar with the node to urge the particles in thedirection of increasing energy density.

In a real fluid, movement of the particle relative to the fluid willalways be opposed by the Stokes forces (which term is used herein toinclude all drag forces experienced by the particle as a result of theirmovement relative to the carrier fluid). Taking the case of a particlesuspended in a uniform fluid which is flowing normal to the axis of astanding wave, i.e. parallel to the nodes of the standing wave, againstan acoustic energy density gradient, a particle at a node will be movedin the direction of the fluid flow if the Stokes forces are greater thanthe acoustic forces in the opposite direction caused by the local energydensity gradient. If the energy gradient fluctuates across the nodalplane the particle will sometimes move faster as it approaches a highenergy zone and sometimes slower as it leaves such a zone but intraversing the node the mean velocity of the particle in the directionof the fluid flow will be identical to that of the fluid. Similarconsiderations apply of course if the body of fluid is stationary andthe standing wave is displaced normal to its axis.

To consider now the case in which the fluid flow and the displacement ofthe high energy zone are mutually perpendicular in the nodal plane,assuming that the Stokes forces attributed to the fluid flow remaingreater than any acoustic forces on the particles in the direction ofthe fluid flow, as the particle encounters an energy density gradient inthe direction of displacement of the high energy zone, one of twoconditions will obtain, as follows:

(1) When the acoustic forces on the particle due to the movement of thegradient exceed the opposing Stokes forces, the particle will move withthe velocity of displacement of the high energy zone so that when thefluid flow carries it out of the standing wave it will have undergone adisplacement due to its entrainment by the acoustic forces acting in thedirection of displacement of the high energy zone.

(2) If movement of the particle at the rate of displacement of the highenergy zone would produce Stokes forces greater than the acoustic forcesthe particle experiences from the steepest energy gradient in the highenergy zone, the particles can no longer be entrained by the movement ofthe zone relative to the standing wave. When the high energy zone hascrossed its path, the particle will have undergone no net displacementwith it.

Thus, by regulation of the parameters and independently of a flow ofcarrier liquid along a nodal plane, it is possible to control themovement within the nodal plane of particles influenced by the acousticenergy, employing the movement of a non-uniformity in the acousticenergy density of the node, or an array of such non-uniformities givinga nodal wave.

If a population of similar particles are subjected to a nodal wave underconditions in which the acoustic and non-acoustic forces are virtuallyin balance individual particles will at different moments either movewith the wave or will be given no net displacement by the wave. Over aperiod of time it will therefore move with an average velocity less thanthat of the wave. This property can be termed the nodal mobility (Mn) ofthe particle and will have a value between 0 and 1 inclusive since it ismade up from a series of instantaneous mobilities of 0 or 1. The rangeof conditions in which a specific particle type will have a nodalmobility less than unity and greater than zero will be small, and infact it is only the inevitable presence of minor disturbances that willprevent an abrupt changeover between these two end values.

Nodal mobility is dependent on the relative velocity between the fieldforce and the nodal wave, so that a particle may simultaneously havedifferent nodal mobilities in two mutually perpendicular directions inthe nodal plane, since both the acoustic gradients and any opposingforces (e.g. Stokes forces or field forces such as gravity orelectromagnetic fields) may be different in each direction. For exampleif in an orthogonal system an xz plane defines the nodal plane and thenodal wave is moving in the x direction, while there is a fluid flow inthe z direction perpendicular to it, a particle can be differently andindependently influenced in each of these directions and so have twonodal mobilities M_(nx) and M_(nz).

This may be contrasted with an arrangement, as in the prior art referredto above, in which to control a group of particles the balance of theacoustic and non-acoustic forces acting simply in the axial direction ofthe standing wave is utilized. The nodes of the wave are treated asessentially uniform acoustic force regions. Although this holds goodonly for the main cross-sectional area of the standing wave and there isan acoustic energy gradient at marginal regions, it has not beensuggested, nor indeed would it be practical to make use of thatvariation to control the movement of particles, if only because suchenergy density gradients are too low.

The present invention can be applied in the manipulation of a widevariety of particulate matter, in which term is intended primarily todenote biological particles ranging from macromolecules (e.g. globularproteins) through viruses, bacteria and yeasts to tissue cell (e.g.plant cells, animal cells and all aggregates), and also inorganic andorganic materials, such as dispersions, suspensions, finely-dividedprecipitates, colloidal and miscella-like systems.

By way of further illustration, aspects of the present invention will bediscussed and exemplified by reference to the accompanying schematicdrawings, in which:

FIG. 1 is a graph illustrating the effects of a changing energy gradienton nodal mobility,

FIGS. 2a and 2b illustrate, respectively, a non-uniform acoustic energygradient with a stepped profile, and the use of this profiled gradientto separate dissimilar types of particles,

FIGS. 3 and 4 are, respectively, a cross-section of an apparatusaccording to the invention and a shadow screen of the apparatus,

FIGS. 5 and 6 illustrate a focussing screen for a modified form of theapparatus in FIG. 3,

FIGS. 7 and 8 are cross-sections of two further forms of apparatusaccording to the invention,

FIG. 9 illustrates a transducer array for generating a nodal wave,

FIGS. 10 and 11 are graphical representations of acoustic energydistributions and gradients in a nodal wave,

FIGS. 12 and 13 are side and plane views of a form of screen intended toproduce asymmetric energy density gradients, and

FIG. 14 is a schematic view of another form of apparatus according tothe invention.

FIG. 1 is a plot of the change of nodal mobility of a series ofdifferent particle types A, B, C, D in relation to acoustic energydensity gradient G. Type A particles are least influenced by theacoustic energy and can move against an energy density gradient in thenodal plane more easily than the other particles types. Particle typesB, C, D are successively more easily held by the standing wave butaround a critical value of the energy density gradient the nodalmobility of each type will change from 0 to 1, there being some spreadat the critical value because of minor disturbances andnon-homogeneities, the latter being likely to be significant amongbiological particles.

Purely for the sake of illustration, numerical values are indicated inFIG. 1 and associated FIGS. 2a and 2b. The nodal mobilities of thedifferent particle types at particular acoustic energy density gradientsfall within bands, the widths of which for each particle type can betabulated as follows:

                  TABLE 2                                                         ______________________________________                                                     Acoustic energy density gradient                                 Particle type  30    40         50  60                                        ______________________________________                                        A              1     1          1   0.9                                                      1     1          1   0.8                                       B              1     1          0.9 0.1                                                      1     1          0.7 0                                         C              1     0.9        0.1 0                                                        1     0.8        0   0                                         D              1     0.3        0   0                                                        0.9   0.2        0   0                                         ______________________________________                                    

FIG. 2a represents an acoustic energy gradient pattern in a nodal planexz of a standing wave in which a nodal wave is produced having atintervals in the z direction a series of stepped changes between thenumerical values given in Table 2 for acoustic energy gradients G_(x)and G_(z) in the x and z directions. Consider such a pattern withreference to FIG. 2b where a mixture of the particle types A, B, C, D isintroduced into the standing wave by a liquid flow in the direction xand the maximum energy density gradient is above the critical values ofthe particle types B, C, D but not that of type A. As will be apparentfrom FIG. 1 and Table 2, at each change of energy density gradient, themagnitude of the gradient drops below the critical value for a furtherparticle type.

When the mixed particle types A, B, C, D enter the standing wave atpoint P the particles of type A are immediately able to pass through thestanding wave with the liquid flow. The remaining particle types B, C, Dare retained by the acoustic energy gradients G_(x), G_(z) but someweakening of the effect on the particles B will cause them to begin tospread in the x direction and slow down in the z direction. When theacoustic energy gradient value then drops below the critical value ofthe B type particles they are released from the standing wave to becarried away in their turn by the liquid flow, and the particle types Cand D are carried off separately in a similar way.

This process thus allows specific particle types to be separated insequence substantially at right angles to a stream of particles, theextent of that stream not being limited by the physical properties ofthe acoustic radiation.

Although the change in energy density gradients along the working pathis shown decreasing in discrete steps to release successive particletypes, in particular instances it may be preferred to employ acontinuous variation, which may be linear or non-linear.

To separate different particle types it is in principle sufficient ifthey are sequentially released by the G_(z) forces to be entrained bythe liquid flow. If still held by the G_(x) forces they will also movewith the liquid but at a slower rate than if released simultaneously bythe change of gradient in both directions, because they then have tofall back in the z direction relative to the nodal wave until they reachzones of smaller G_(x) gradients.

For maximum discrimination between the different particle types the twogradients G_(x), G_(x) are equal so that for any particle type bothM_(nx) and M_(nz) tend to 0 to 1 together, and the nodal wave velocity(V_(nw)) in the z direction should match the mean liquid flow velocity(V₁) in the x direction, i.e. ##EQU1##

A variety of means may be employed to generate and move nodal waves,both mechanical and electronic. A simple mechanical method is to cast aset of acoustic shadows which pass along a vessel, the shadow edgesmoving in the nodal plane, whether perpendicular or parallel or obilqueto the fluid flow. At frequencies appropriate for a liquid medium suchas water (i.e. upwards of about 500 KHz) relatively sharp shadows areobtainable; the higher the frequency the sharper the acoustic shadows,and frequencies in the MHz range will be usually be preferred.

An example of the use of a screen to produce such shadows is shown inthe apparatus of FIGS. 3 and 4. In FIG. 3 can be seen in cross-section atank 10 containing a suitable liquid to provide an acoustic coupling forbarium zirconate titanate transducers 12 mounted at parallel oppositesides of the tank are at a suitable distance from a working column 14immersed in the tank liquid and extending parallel to said sides of thetank within the length of the tank. The column has sides walls 16transparent to the ultrasound frequency of the transducers. Tofacilitate observation, the end walls 18 and possibly also the sidewalls are transparent to light. The column is located within a shadowscreen 20 that has side walls parallel to and almost touching the sidewalls 16 of the column.

The side walls of the screen comprise a series of parallel alternatingvertical tongues 22 and slots 24 and the screen is of a material thatreflects the ultrasound frequency employed. The tongues of opposite sidewalls are coincident with respect to the axis of propagation of thetransducers 12. The screen thus provides alternate sections in whicheither the column is shielded from the ultrasonic transmission byopposite pairs of tongues 22, or is exposed to the ultrasoundtransmission passing unimpeded into the column through the interveningslots 24. An array of sharp-edged acoustic shadows are thereby formed inthe standing wave produced by interference of the ultrasoundtransmissions entering the column through the slots. The shadows will begiven a width and a spacing such as to ensure a series of spacedcolumn-like standing waves is created in the working chamber between thesuccessive spaces. Of particular importance is the sharpness of theshadow edges which determines the energy gradient. Since an ultrasonicbeam is never fully collimated, some of the energy passing through theslots 24 will reflect off the inside surfaces of the tongues 22. If itis necessary to prevent the formation of a standing wave betweenopposing tongues by mutual reflection, the distance between the facingsurfaces of the tongues should be an odd multiple of the quarter wavelength.

FIGS. 5 and 6 show, for an apparatus otherwise similar to that in FIG.3, a screen 40 enclosing opposite sides of the column 14 with itstransparent side walls 16. In this instance, the screen is one withwhich nodal waves can be formed by refracting or focussing acousticenergy to produce a non-uniform energy density. It has walls 42 whichare continuous and of a material having different acoustic transmissionproperties to those of the bath liquid at the wavelength of theultrasound transmission. Formed on one or both of the surfaces of walls42 is a grid of depressions 44, which may be spherical, the radius ofcurvature being chosen so as to cause a uniform incident transmission ofultrasound to form sharply converging beams as it passes through to thecolumn 14. The spherical depressions in the opposing walls of the screenare aligned with each other so that the opposed converging beams in thecolumn 14 are coaxial.

Focussing screens to provide the required acoustic energy gradients mayof course have many different surface configurations, e.g. withpart-cylindrical depressions to produce non-uniform acoustic densitiesin one direction only in the nodal plane.

Movement of screens such as those described above at an appropriateconstant velocity (or such movement of the liquid carrying theparticles) will allow the acoustic energy gradients to move particlesrelative to the liquid. Depending upon the form of the apparatus and theprocess to be operated in it, that may be a suitable form ofdisplacement to employ, but other forms of displacement can be providedif required. Thus, after a movement over a distance equal to orexceeding the spacing between successive elements of the array ofelements in the walls of the screen, the screen can be returned at afaster rate to its starting position. The object of this quick return isto transfer particles to the energy gradients associated with asucceeding element when their return movement with the screen is opposedby the great Stokes forces related to the increased return velocity. Theconditions are such that the particles are swept from the energygradients on which they have been held. The particles are thusprogressed along the length of the screen by continued repetition ofthis cycle of movement. As will be appreciated in the numerical examplegiven with FIGS. 3 and 4, the screen may need an oscillation of only oneor two millimeters.

Since a screen such as that shown in FIGS. 5 and 6 can be static if theliquid column 16 is moved instead, it will be clear that a discretescreen element is not then required. This leads to the possibility ofcoupling the ultrasonic transducer to the working liquid through anacoustic coupling block that is configured to provide the requiredfocussing effect. Acoustic coupling blocks of metal, e.g. aluminiumalloy, are themselves known; to provide a focussing effect similar tothat described with reference to that described with reference to FIGS.5 and 6 the interface between the distal end of the coupling block andthe liquid is given a series of, e.g. spherical, depressionscorresponding to the depressions A4 of FIG. 5, whereby each suchdepression similarly focusses the ultrasound entering the liquid. A wallat the opposite side of the liquid column has similar depressions,coaxial with those of the coupling block. With that wall surface at anappropriate spacing from the coupling block, the nodal surfaces of thestanding wave will contain sharp energy gradients. It should be notedthat the dimensions of the lens elements must be longer than thewavelength of the ultrasound in the metal.

Ceramic transducers can be easily and cheaply produced in a wide rangeof sizes and shapes, and these ferroelectrics require only modestvoltages to provide useful power. It is therefore practical to userelatively large scale cylindrical transducers to provide cylindricalnodal surfaces. FIG. 7 shows in cross-section a tubular column 50 havingconcentric cylindrical side walls 52 spaced apart a short distance, say5 mm, but enclosing an annular space of much greater depth. A septum 54completely blocks the annular space at one point in its circumferentialextent. Cylindrical ceramic transducers 56 (shown in the first quadrantonly) extend coaxially around the column. A cylindrical shadow screen 58(shown in the second quadrant only), also coaxial with the column, hasslotted walls as previously described, the slots extending axially ofthe column. Means (not shown) are provided to oscillate the screen aboutthe axis of the column.

Ports 60 are positioned as required, at various points around thecircumferential extent of the column to provide liquid inlets andoutlets for establishing different liquid flow velocity regimes indifferent parts of the column so that the differential separation effectalready described with reference to FIG. 1 can be obtained withoutvarying the rate of progression of the nodal waves.

The cylindrical configuration may also be used if it is required toproduce a continuously moving train of nodal waves, this being possibleby a continuous, uniform displacement of the screen.

Where the apparatus employs a shadow screen, as in the examples of FIGS.2 and 3 and FIG. 7 it is possible to combine the screen and the workingchamber walls, the opposed walls through which the acoustic energy is tobe transmitted then being formed from alternate strips of transmittingand reflecting materials, e.g. polymethyl methacrylate or polystyrenefor the former and tungsten or aluminium for the latter. The ports canbe set in the reflecting strips to extend over at least a substantialpart of the axial length of the column. As another alternative, it maybe desirable to position a shadow screen within the working column.Putting an oscillating screen at the side walls of the column themovement of the screen can help to prevent particles becoming attachedto the side walls and can generate sharper shadows than if outside thewalls.

The preceding examples use two opposed transducers, which allow theenergy intensity of the transmissions forming the standing wave to bematched sufficiently closely in a limited region to avoid acousticstreaming in substance, but as already indicated a greater degree ofacoustic streaming can be tolerated if the particles are not beingmanipulated by acoustic forces acting along the axis of the standingwave. Thus, it is possible to operate with an ultrasonic transducer onlyat one side of a working space, if that space is not too wide and a highefficiency reflection surface is placed close to its opposite side.

FIG. 8 shows in cross section a column 70 set in a liquid bath 72 atsome distance from and parallel to a ceramic transducer 74 extending thefull length of the column, the bath liquid providing acoustic couplingbetween the transducers and the column. The column has a side wall 76transparent to ultrasound at the operating frequency of the transducerand an opposite side wall 78 which is a highly efficient reflector.Conveniently, the side wall 78 is also transparent to light to allow theinterior of the column to be viewed; for example, it could be composedof a glass plate 80 of a thickness to reflect the ultrasound and backedby an air space 82 formed with a further glass plate 84. Alternatively,side wall 76 and screen 86 can be transparent to light, if the reflectoris opaque.

Immediately in front of the column 70 is a shadow screen 86 arranged tobe displaced as already described by means (not shown). The transmissionfrom the tranducer is thus reflected from the plate 80 to form astanding wave by interaction with the incident transmission from thetransducer with only a moderate degree of acoustic streaming resultingfrom the inevitable imbalance of the incident and reflected waves.

It will be understood that the geometry of the device can be varied,e.g. to the cylindrical configuration already described.

Nodal waves may also be generated and displaced electronically bycontrol of an array of transducers set side by side and, indeed, asingle ultrasonic transducer can produce different oscillations in asequence of zones electrically isolated from each other. FIG. 9 shows asurface of a rectangular ceramic transducer 90 in which the elctricallyconductive coating on the reverse side is continuous but that on thefront face is divided into strips 92 electrically isolated from eachother. The whole transducer is of uniform thickness and thus has auniform resonant frequency, i.e. the resonant frequency of each strip 92is the same.

When two such transducer mosaics are arranged parallel and face to facewith opposing strips electrically energised, a standing wave isgenerated between them by the two interfering beams. These beams exhibita small degree of divergence, and the width of each strip must besomewhat narrower than the diverging fringe of the ultrasonic beamoverlapping it from an adjacent strip. The divergence angle depends onthe geometry of the strip, the frequency of the ultrasound and thedistance between the transducer face and the working volume.

The individual strips have separated electrical switching connections 94so that a selected group of the strips can be energised together, andthe energised regions can be displaced along the array by appropriateswitching means (not shown) acting through the electrical connections tobring the strips into and out of operation sequentially. When the arrayson either side of a working space are energised synchronously in such asequence, it is possible to generate a standing wave that effectivelymoves along the column.

This may be exemplified by reference to FIG. 9 with the series of strips92 numbered 1 to 9. It can be assumed that a corresponding transducermosaic is directly opposite this illustrated mosaic. Opposed pairs ofstrips of the two mosaics are controlled to switch simultaneously, andthe following description will refer, for simplicity, to the operationof only one series.

If initially the strips 3 and 4 are operating, the divergence of thebeams generated by these strips generates energy gradients in the spaceadjacent to the volume that lies directly between them, that is, thesegradients extend to the space opposite strips 2 and 5. If strip 3 isde-energised, particles held in the standing wave in the volume betweenthis strip and its opposite number are no longer in a high energy field,but are in the energy gradient associated with the periphery of the beamgenerated by the strip 4. The particles influenced by the acousticenergy will therefore move up the energy gradient towards the areas ofmaximum energy density, that is, towards the middle of the fieldgenerated by a strip 4. Strip 5 is next energised, and then strip 4 isdeenergised so that the energy gradient is again displaced. Thisprocedure is continued along the successive strips to progress theparticles through the working volume.

The transducers shown in the preceding examples have been spaced somedistance from the working volume which can thus be assumed to be in thefar field of the energy propagation from the transducers. However, it isalso possible to make use of the pheomenon that at a point in spaceclose to a radiating surface the emissions from that surface will havesignificant phase differences due to the Fresnel diffraction pattern.This creates in the near field a complex pattern of domains of high andlow acoustic energy density. With increase of distance from theradiation source, that no longer happens and in the far field, in whicha Fraunhofer diffraction pattern is established, the acoustic field isuniform, decreasing slowly depending on beam spread and attenuation.Since the operation of a device according to the present inventionrequires acoustic energy density gradients in a nodal surface, bymatching of the energy distribution in the near Fresnel field with thatfrom a second transducer placed closed to and in face to face relationwith the first transducer, a standing wave is produced. In that standingwave there are acoustic energy gradients which, acting on particlesresponsive to these gradients, group the particles in planar regionsthat can be identified as the nodal planes of the field, albeit thatthere are wider variations of energy intensity in these planes by virtueof the Fresnel diffraction fields that prevail. Similarly, the Fresnelfield form a simple transducer can be reflected back to that transducerto produce like acoustic energy density gradients. Near field systemssuch as these containing appropriate energy density gradients may beemployed, e.g., with the cylindrical configuration shown in FIG. 6.

The sharp lateral variations in acoustic intensity in the near field mayalso be employed to form a standing wave by reflection. A reflector isplaced parallel to the emitting surface of the transducer and in itsnear field such that the high intensity regions of the primary radiationcoincide with other intensity regions of the reflected radiation, andthere is a similar conicidence of low intensity regions.

The forces acting on a particle on either side of a nodal plane in astanding wave are necessarily symmetrical in magnitude but opposite indirection. However, a nodal wave, being a progression of variations inthe energy density of the standing wave in the plane of a node, can haveasymmetric energy density gradient and that can be put to use in theoperation of the present invention.

FIG. 10 shows in its upper part a symmetrical distribution of acousticenergy density in the z direction to either side of a point of maximumenergy density. Below this is shown the magnitude and direction of thegradients in the energy density distribution, these energy densitygradients being a measure of the net acoustic force on a particle.

On the left hand side of the gradient plot the scale shows the size andthe direction of the forces on the particle when no relative motionexists between the high energy zone and the liquid. On the right handside the scale shows the net forces on a particles when a Stokes forcedue to a constant velocity fluid flow from left to right is added to theacoustic forces. In the latter instance, the particle will come to restin position z₁ along the z axis. By reversing the direction of theliquid flow without changing its magnitude, the particle will move toposition z₂.

In contrast to FIG. 10, FIG. 11 shows an example of an asymmetricdistribution of energy density in the z direction about a point ofmaximum energy density, and also shown are the magnitude and directionof the gradients and thus the acoustic forces on a particle.

With no relative motion between the high acoustic energy domain and theliquid, the particle will move to position z on the z axis wherein theenergy density is greatest. If a positive Stokes force is added to theacoustic force by relative movement of the liquid to the right, theparticle will move to position z₁ where the net forces acting on it arenow zero. It is clear from FIG. 11 that by reversing the relativemovement without changing its magnitude, the particle will be releasedfrom the nodal wave and will move to the left and out of the region ofhigher energy density. There is therefore a means of moving particles inone direction even when there are equal cyclic movements in oppositedirections between the standing wave and the liquid.

Thus, to move particles using nodal waves by the ratchet method asdescribed in relation to FIGS. 3 and 4 it is possible to employ eithersymmetrical energy gradients and asymmetric motion, or asymmetic energygradients and symmetrical motion, e.g. sinusoidal, or a combination ofboth.

FIGS. 12 and 13 illustrate an example of the use of asymmetric gradientsproduced by a shadow screen whose leading and trailing edges are notequally sharp. It shows a part of a column 102 having side walls 104which are transparent to ultrasound at the frequency used. An acousticshadow screen 106 comprises opposed arrays of walls 108 set obilquely tothe axis of column 102 such as to provide in effect to a set of slotsformed between the inner edge 110 of each wall 108 and the outer edge112 of the wall immediately above it. The inner edges 110 are close tothe column 102. Short flanges 114 projecting from the outer edgesprevent sound reflecting from most of the length of each wall into thecolumn. Strip ceramic transducers 116 set at an appropriate distanceparallel to the column and energised by a common signal source provide astanding wave through the slots in the screen to generate a series ofnodal planes within the column which have asymmetric energy densitygradients.

By moving the screen upwards, particles are moved with the nodal waves,but when the screen is moved downwards, particles are not moved. If thescreen oscillates symmetrically about a mean position with an amplitudewhich equals or exceeds the distance between the slots in the screen,particles will progress upwards. Alternatively, the screen may remainedfixed while the column oscillates symmetrically with the same amplitude.

As a further example, FIG. 14 illustrates an apparatus according to theinvention using a standing wave set up in the near field by reflection.

A water-filled vessel 120 is shown mounted on supports 122. Projectinginto one side of the vessel is a housing 124 of Dural (British StandardHE15HF) for a 25 mm diameter transducer type PC5 (Unilator Limited,Wrexham Clwyd, Wales) acoustically coupled to a 17 mm diameter block 128that is an integral part of the Dural housing. The operating frequencyof the transducer 126 is 2.100 MHz. The block has a thickness of 9.09mm, with a sonic velocity in the alloy of 6400 m/s. This corresponds to5.97 halfwave lengths, i.e. sufficiently close to an integral number ofhalfwave lengths to provide essentially maximum transmission, while thedistance is short enough to ensure that the block occupies less thanhalf the axial length of the near field (in which Fresnel diffractiondetermines the spatial distribution of energy). The acoustic couplingbetween the transducer and the water is obtained using a water-basedcouplant (Ultragel from Diagnostic Sonar Limited, Houston, Scotland).

Into the opposite side of the vessel there projects a Dural rod 132 onthe face of which is mounted a tungsten plate 134, 17 mm diameter and1.00 mm thick, with its face at a spacing of 4.947 mm from the couplingblock, the opposed faces of the plate and the block being parallel andcoaxial. As the sonic velocity in the water of the vessel if 1484 m/s at20° C., at the transducer frequency the gap between the block and theplate accommodates 14 halfwave lengths, so promoting a standing wavehaving a standing wave ratio of 1.0.

On the mounting 140 above the vessel there is suspended a rectangularchamber 142 having acoustic windows of 3-micron mylar polyester filmfacing the block and the plate. The chamber is provided with inlet andoutlet porting (not shown) for a continuous through-flow but in theexperiment to be described the porting was closed after a suspension of1% by weight of 6 micron polystyrene microspheres in water was placed inthe chamber.

This mounting 140 comprises guides 144 running between rollers 146 forlinear movement of the chamber into and out of the vessel parallel tothe block and the plate.

With the transducer energised the chamber was displaced on the rollersto pass through the resonant cavity between the block and the plate. Thewalls of the vessel and of the chamber parallel to the plane of thedrawing were transparent, permitting observation of the contents of thechamber through a tele-microscope and it was observed that the particlesin the chambers retained their positions relative to the acoustic field,independently of the movement of the chamber. Thus, as the chamber waswithdrawn vertically from the vessel at a speed of 1 mm/s the particlesresisted the Stokes forces of the carrier fluid to remain fixed in spaceand thus separate from the suspension to collect as a dense deposit atthe base of the chamber.

I claim:
 1. A method of manipulating particles in a fluid medium,comprising the steps of:(a) injecting ultrasonic energy into a fluidmedium and establishing an ultrasonic standing wave in the medium; (b)choosing standing wave characteristics of said standing wave in relationto the particles so as to accumulate at least a portion of the particlesat least at one nodal plane of the standing wave in the fluid medium;(c) giving a varying spatial energy density distribution to saidstanding wave in at least one of its at least one nodal planes in thefluid medium; and (d) controlling positions of the particles in said atleast one nodal plane by the varying energy density of the standing wavein each said at least one nodal plane.
 2. A method according to claim 1wherein said controlling positions step includes maintaining each saidparticle substantially fixed in position in relation to the varyingenergy density distribution of its at least one nodal plane, against arelative displacement between the standing wave and the fluid medium inthe direction of said at least one nodal plane.
 3. A method according toclaim 1 wherein said controlling positions step includes displacing theparticles along said at least one nodal plane relative to the varyingenergy density therein by means of at least one force selected from thegroup consisting of the viscosity forces of the fluid medium withrespect to the particles, and field forces, said at least one forcehaving at least a component acting in the direction of said at least onenodal plane.
 4. A method according to claim 1 wherein the standing wavehas said varying energy density distribution in mutually transversedirections, parallel to the at least one nodal plane, to influence theparticles independently in each said direction.
 5. A method according toclaim 1 wherein each of the at least one nodal planes are curved.
 6. Amethod according to claim 1 wherein said giving a varying energy densitycomprises using a change of density at the edge of an acoustic beam toprovide said varying energy density.
 7. A method according to claim 1wherein the varying of acoustic density is produced as a spatiallyrepeated pattern in each of said at least one nodal plane.
 8. A methodaccording to claim 1 comprising the step of establishing a near fieldregion of the standing wave in the fluid medium to provide said varyingenergy density in at least one of said at least one nodal planes.
 9. Amethod according to claim 1 comprising the further steps of generating arelative reciprocatory movement between the standing wave and the fluidmedium parallel to the said at least one nodal plane, and generating atleast one different parameter from the group consisting of (a) velocityof movement and (b) acoustic gradient that has different magnitudes inthe opposite directions of reciprocation whereby to produce a netdirectional effect for effecting said control of the movement of theparticles in one of said directions.
 10. Apparatus for manipulatingparticles in a fluid medium comprising:a chamber for containing thefluid with particles suspended in the fluid; means for generating anultrasonic standing wave having at least one nodal plane in the chamber;and means for giving said standing wave a non-uniform spatial energydensity distribution in said at least one nodal plane, whereby in adirection parallel to said at least one nodal plane at least aproportion of the particles are controlled by the action of saidnon-uniform energy density in relation to non-acoustic forces actingparallel to said least one nodal plane.
 11. Apparatus according to claim10 wherein the chamber has opposed walls parallel to the at least onenodal plane.
 12. Apparatus according to claim 10 wherein the chamber isin the form of a body of revolution and the at least one nodal plane arecurved substantially coaxially with the chamber curvature.
 13. Apparatusaccording to claim 10 further comprising screening means between saidgenerating means and said particle-containing fluid to give saidnon-uniform energy density distribution.
 14. Apparatus according toclaim 13 wherein the screening means comprise alternate ultrasonictransmitting and non-transmitting elements.
 15. Apparatus according toclaim 13 wherein the screening means comprise at least one diffractingelement for the energy propagation.
 16. Apparatus according to claim 15wherein said at least one diffracting element is integrally formed on acoupling member that couples the acoustic generating means to the fluidmedium.
 17. Apparatus according to claim 13 wherein the screening meansforms at least one boundary of said chamber.
 18. Apparatus according toclaim 10 comprising an array of ultrasonic transducers and means forenergizing said transducers in sequence to generate a standing wave thathas a variation of energy density in said at least one nodal plane witha distribution that is time-dependent whereby to cause displacement ofat least one density peak in the direction of the at least one nodalplane.
 19. Apparatus according to claim 10 wherein the chamber is in theform of a coil and the at least one nodal plane are curved substantiallycoaxially with the chamber curvature.